Yuri Ann Saito's long-term research objective is to understand the pathophysiology of functional gastrointestinal disorders so that effective treatments may be found for this common disorder that affects 10- 20% of the population. She believes that this can be achieved in part through the use of advanced epidemiological methods. The K23 Mentored Patient-Oriented Research Career Development Award would provide an excellent opportunity to gain experience in conducting high-quality epidemiological and genetic epidemiological research in functional gastrointestinal diseases. The proposed research plan is targeted toward expanding our basic understanding of why irritable bowel syndrome (IBS) appears to cluster in families, and to evaluate the environmental and possible genetic factors contributing to IBS. A combined case-control and family study is proposed where questionnaire data will be collected from 500 clinic-based patients with IBS, 500 clinic-based controls, and approximately 5000 first-degree relatives. The aims of this study are geared to answer whether IBS truly aggregates in families, what are the characteristics of familial IBS, and whether IBS transmission in families follows a genetic pattern. Thus, this study composed of 3 complementary sections: a familial aggregation study, classification regression tree (CART) analysis to identify clinical and epidemiological features of familial IBS, and complex segregation analysis to determine whether there is evidence of a major gene for IBS. This study's significance is that it will provide meaningful scientific data that would justify future genetic studies including a more extended biospecimen-based study with a search for candidate genes. The study will also provide insight into the non-genetic factors that lead to IBS and its variable manifestations. This career award would build upon her previous experience using survey-based data to study clinic patients and the community and her M.P.H. It would allow her to obtain training in genetic epidemiology, statistical genetics, and genetics through coursework, attending seminars, and through the project itself at an institution rich in clinical and epidemiological research resources. The additional training and the data generated from this research career development award would ensure that she would advance her academic career, successfully compete for independent peer-reviewed funding, and make significant scientific contributions to the understanding of this and other gastrointestinal disorders.